Melatonin Mitigates iNOS-Related Effects of HEMA and Camphorquinone in Human Dental Pulp Cells: Relevance for Postoperative Sensitivity Mechanism in Type 2 Diabetes.

High elution and diffusion of 2-hydroxylethyl methacrylate (HEMA) and camphorquinone (CQ) through dentinal tubules may induce pulp injury and postoperative sensitivity. We aimed to investigate the melatonin protective effect in HEMA- and CQ-treated human dental pulp cells (hDPCs) as well as its relevance in a mechanism for postoperative sensitivity in diabetic patients. hDPCs were exposed to HEMA (5 mM) and/or CQ (1 mM) in the absence and presence of melatonin (MEL) (0.1 mM and 1 mM). Heme oxygenase-1 (HMOX1), NADPH oxidase-4 (NOX4), BCL-2-associated X-protein (BAX), B-cell lymphoma-2 (BCL-2) and caspase-3 (CASP3) gene expression levels, and superoxide dismutase (SOD) activity were measured in hDPCs while inducible nitric oxide synthase (iNOS) and melatonin protein expression were measured in human dental pulp as well, by RT-PCR, by ELISA, and spectrophotometrically. Bioinformatic analyses were performed by using the ShinyGO (v.0.75) application. Type 2 diabetic patients showed a higher incidence of postoperative sensitivity and lower melatonin and higher iNOS content in dental pulp tissue compared with non-diabetic patients. Melatonin, when co-added in hDPC culture, reverses HEMA and CQ cytotoxic effects via anti-apoptotic and anti-inflammatory/antioxidant iNOS-related effects. Enrichment analyses showed that genes/proteins, altered by HEMA and CQ and normalized by melatonin, are the most prominently overrepresented in type 2 diabetes mellitus pathways and that they share subcellular localization in different oligomeric protein complexes consisting of anti- and pro-apoptotic regulators. This is the first evidence of the ability of melatonin to counteract iNOS-mediated inflammatory and stress effects in HEMA- and CQ-treated hDPCs, which could be of significance for the modulation of presently observed immediate postoperative sensitivity after composite restoration in type 2 diabetic patients.

PDGF inhibits BMP2-induced bone healing.

Bone regeneration depends on a pool of bone/cartilage stem/progenitor cells and signaling mechanisms regulating their differentiation. Using in vitro approach, we have shown that PDGF signaling through PDGFRß inhibits BMP2-induced osteogenesis, and significantly attenuates expression of BMP2 target genes. We evaluated outcomes of treatment with two anabolic agents, PDGF and BMP2 using different bone healing models. Targeted deletion of PDGFRß in αSMA osteoprogenitors, led to increased callus bone mass, resulting in improved biomechanical properties of fractures. In critical size bone defects BMP2 treatment increased proportion of osteoprogenitors, while the combined treatment of PDGF BB with BMP2 decreased progenitor number at the injury site. BMP2 treatment induced significant bone formation and increased number of osteoblasts, while in contrast combined treatment with PDGF BB decreased osteoblast numbers. This is in vivo study showing that PDGF inhibits BMP2-induced osteogenesis, but inhibiting PDGF signaling early in healing process does not improve BMP2-induced bone healing.

Bone microRNA-21 as surgical stress parameter is associated with third molar postoperative discomfort.

OBJECTIVE: To evaluate an association between bone levels of inflammation/oxidative stress mediators and postoperative discomfort after third molar conventional or piezosurgery. MATERIAL AND METHODS: Twenty-six subjects with bilaterally impacted mandibular third molars, who underwent either piezo or conventional surgery, were included in a split-mouth design study. MicroRNA-21 (miR-21) expression, interleukin-1 beta (IL-1ß), and vascular endothelial growth factor (VEGF) proteins, as well as superoxide dismutase (SOD) activity in alveolar bone, were evaluated. Pain intensity, the first pain appearance, analgesic first use and total dose taken, trismus, and swelling were clinically recorded. RESULTS: MiR-21 expression was higher while VEGF protein was lower in piezosurgery vs. conventional groups. The differences in IL-1ß protein and SOD activity were not significant between groups. The pain intensity on the first day was significantly decreased in piezosurgery group. The first pain appearance and the first analgesic taken were reported sooner in conventional vs. piezosurgical group. Significantly pronounced trismus on the third day following conventional surgery was found. In conventional group, significantly increased trismus was observed on the third compared to the first postoperative day. MiR-21 showed significant correlation with the first pain appearance. CONCLUSION: Delayed onset of less pronounced postoperative pain after piezosurgical vs. conventional extraction of impacted lower third molar was significantly associated with expression of bone miR-21. CLINICAL RELEVANCE: Alveolar bone miR-21 may reflect surgical stress and is associated with third molar postoperative pain onset.

Group 5 ITI Consensus Report: Digital technologies.

OBJECTIVES: Working Group 5 was assigned the task to review the current knowledge in the area of digital technologies. Focused questions on accuracy of linear measurements when using CBCT, digital vs. conventional implant planning, using digital vs. conventional impressions and assessing the accuracy of static computer-aided implant surgery (s-CAIS) and patient-related outcome measurements when using s-CAIS were addressed. MATERIALS AND METHODS: The literature was systematically searched, and in total, 232 articles were selected and critically reviewed following PRISMA guidelines. Four systematic reviews were produced in the four subject areas and amply discussed in the group. After emendation, they were presented to the plenary where after further modification, they were accepted. RESULTS: Static computer-aided surgery (s-CAIS), in terms of pain & discomfort, economics and intraoperative complications, is beneficial compared with conventional implant surgery. When using s-CAIS in partially edentulous cases, a higher level of accuracy can be achieved when compared to fully edentulous cases. When using an intraoral scanner in edentulous cases, the results are dependent on the protocol that has been followed. The accuracy of measurements on CBCT scans is software dependent. CONCLUSIONS: Because the precision intraoral scans and of measurements on CBCT scans and is not high enough to allow for the required accuracy, s-CAIS should be considered as an additional tool for comprehensive diagnosis, treatment planning, and surgical procedures. Flapless s-CAIS can lead to implant placement outside of the zone of keratinized mucosa and thus must be executed with utmost care.

Efficacy and safety of 1% ropivacaine for postoperative analgesia after lower third molar surgery: a prospective, randomized, double-blinded clinical study.

OBJECTIVES: The purpose of this study was to investigate postoperative analgesic effect of ropivacaine administered as main or supplemental injection for the inferior alveolar nerve block (IANB) in patients undergoing lower third molar surgery. MATERIALS AND METHODS: The double-blind randomized study comprised 72 healthy patients. All patients received two blocks, the IANB for surgical procedure + IANB after surgery for postoperative pain control, and were divided into three groups: (1) 2 % lidocaine/epinephrine + 1 % ropivacaine, (2) 2 % lidocaine/epinephrine + saline, and (3) 1 % ropivacaine + saline. The occurrence of postoperative pain, pain intensity and analgesic requirements were recorded. Data were statistically analyzed using chi-square, Fisher, and Kruskal-Wallis tests and analysis of variance (ANOVA) with Bonferroni and Tukey correction. RESULTS: Ropivacaine was more successful than lidocaine/epinephrine in obtaining duration of postoperative analgesia, reduction of pain, and analgesic requirements whether ropivacaine was used for surgical block or administered as a supplemental injection after surgery. CONCLUSIONS: Ropivacaine (1 %, 2 ml) resulted in effective postoperative analgesia after lower third molar surgery. CLINICAL RELEVANCE: Since pain control related to third molar surgery requires the effective surgical anesthesia and postoperative analgesia, the use of 1 % ropivacaine could be clinically relevant in a selection of appropriate pain control regimen for both surgical procedure and early postsurgical treatment.

Apical root-end filling with tricalcium silicate-based cement in a patient with diabetes mellitus: A case report.

Introduction: The material used for root-end filling has to be biocompatible with adjacent periapical tissue and to stimulate its regenerative processes. Tricalcium silicate cement (TSC), as a new dental material, shows good sealing properties with dentin, high compression strengths and better marginal adaptation than commonly used root-end filling materials. Although optimal postoperative healing of periapical tissues is mainly influenced by characteristics of end-root material used, it could sometimes be affected by the influence of systemic diseases, such as diabetes mellitus (DM). Case report: We presented apical healing of the upper central incisor, retrofilled with TSC, in a diabetic patient (type 2 DM) with peripheral neuropathy. Standard root-end resection of upper central incisor was accompanied by retropreparation using ultrasonic retrotips to the depth of 3 mm and retrofilling with TSC. Post-operatively, the surgical wound healed uneventfully. However, the patient reported undefined dull pain in the operated area that could possibly be attributed to undiagnosed intraoral diabetic peripheral neuropathy, what was evaluated clinically. Conclusion: Although TSC presents a suitable material for apical root-end filling in the treatment of chronic periradicular lesions a possible presence of systemic diseases, like type 2 DM, has to be considered in the treatment outcome estimation.

Quality of analgesia after lower third molar surgery: A randomised, double-blind study of levobupivacaine, bupivacaine and lidocaine with epinephrine.

BACKGROUND/AIM: Surgical extraction of lower third molars is followed by mild or severe postoperative pain which peaks at maximal intensity in the first 12 hours and has a significant impact on a patient's postoperative quality of life. The use of long-acting local anaesthetics is a promising strategy to improve postoperative analgesia. The aim of the present study was to investigate analgesic parameters and patient satisfaction after using 0.5% levobupivacaine (Lbup), 0.5% bupivacaine (Bup) and 2% lidocaine with epinephrine 1:80,000 (Lid + Epi) for an inferior alveolar nerve block following lower third molar surgery. METHODS: A total of 102 patients (ASA I) were divided into three groups, each of which received either 3 mL of Lbup, Bup or Lid + Epi. The intensity of postoperative analgesia was measured using a verbal rating scale (VRS). The total amounts of rescue analgesics were recorded on the first and during seven postoperative days. Patients satisfaction was noted using a modified verbal scales. RESULTS: A significantly higher level of postoperative pain was recorded in Lid + Epi group compared to Bup and Lbup groups. No significant differences were seen between Bup and Lbup, but a significant reduction in the need for rescue analgesics was seen postoperatively in both Lbup and Bup (50%) in comparison with Lid + Epi (80%) in the first 24 hours. The same significant trend in rescue analgesic consumption was recorded for seven postoperative days. Patients' overall satisfaction was significantly lower for Lid + Epi (10%) than for Lbup (56%) and Bup (52%). CONCLUSION: The use of a new and long-acting local anaesthetic 0.5% levobupivacaine is clinically relevant and effective for an inferior alveolar nerve block and postoperative pain control after third molar surgery. In our study Lbup and Bup controled postoperative pain more efficiently after lower third molar surgery compared to Lid + Epi.